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▎Alzheimer's disease (AD), editor of WuXi AppTec's content team, is the most common neurodegenerative disease among the elderly.
It has a profound impact on patients, their families, and society
.
Moreover, the progress of drug development in this field is slow, and it is urgent to explore innovative strategies for new drug development
.
In a study published in Nature Aging today, the team of Professor Huang Yadong from the Gladstone Institutes in the United States found that an "old drug" that has been on the market for nearly 40 years can relieve cognition in animal experiments And learning deficits
.
And analysis of real-world patient data using this drug shows that among the elderly over 65, people who regularly take this drug have a 35%-75% reduction in the risk of developing Alzheimer's disease
.
The researchers pointed out that the results of this study reveal a new strategy for drug development
.
The development of new drugs for complex diseases such as Alzheimer's disease has always been a time-consuming and labor-intensive process
.
In order to bring safe and effective therapies to patients faster, the Gladstone Institute launched the Gladstone Center for Translational Advancement in 2017 to explore new uses of "old drugs" that have been approved by the FDA
.
The primary goal of this center is to develop treatments for Alzheimer's disease.
Due to the complexity of its etiology, the strategy adopted by the research team does not target specific signaling pathways, but comprehensively detects differences in gene expression between patients and healthy people.
, Including patients with different APOE alleles
.
The different forms of the APOE gene are one of the most important genetic risk factors for Alzheimer's disease.
People who carry two APOE4 alleles have an increased risk of 12-14 compared with those who do not carry APOE4 alleles.
Times! The researchers found that the expression levels of nearly 2,000 genes in patients changed, and about 6% of the genes had similar changes in patients carrying different combinations of APOE3 and APOE4 alleles
.
▲Similar gene expression changes were found in Alzheimer's disease patients carrying different combinations of APOE3 and APOE4 alleles (picture source: reference [2]).
Then, the researchers conducted a study on more than 1,300 approved drugs.
After screening, take a look at which drugs can reverse these changes in gene expression
.
The screening results found a drug called bumetanide, which is a diuretic that has been used in the past few decades to reduce edema caused by heart failure, liver or kidney disease
.
Bumetanide can regulate the ability of cells to absorb sodium and chloride ions.
In addition to regulating the body's water balance, it also plays an important role in transmitting electrical signals to nerve cells in the brain
.
In a mouse model of Alzheimer's disease carrying two APOE4 alleles, scientists found that bumetanide can significantly delay the onset of Alzheimer's disease symptoms
.
Usually these mice developed learning and memory deficits at 15 months (equivalent to 60 years old in humans), but the animals treated with bumetanide did not develop these deficits
.
In addition, in another mouse model, bumetanide treatment also reduced the degree of amyloid deposition in the animal's hippocampus (one of the key areas in the brain for memory production)
.
▲The treatment of bumetanide (right) reduces the deposition level of amyloid in Alzheimer's disease mouse model (picture source: reference [2]) Traditional drug development is after animal research, usually in human clinical The safety of the drug is tested in detail in the trial
.
However, bumetanide has been approved by the FDA, which allows researchers to analyze its use data in the real world and observe its possible therapeutic effects
.
Researchers analyzed the patient databases of the University of California, San Francisco (UCSF) and Mount Sinai Health System (Mount Sinai Health System) and found more than 3,700 bumetanide over the age of 65
.
Then compare them with the incidence of Alzheimer's disease in elderly people of similar age and health, but using other diuretics
.
Researchers have found that patients taking bumetanide have a 35% to 75% reduction in disease risk
.
▲The risk of Alzheimer's disease in elderly people taking bumetanide is significantly reduced (picture source: reference [3]) "These two electronic health record databases did not affect patients based on their APOE allele characteristics.
Classification, which means that bumetanide may benefit a wide range of patients who carry two APOE4 alleles
.
"Senior author of this study and senior researcher Professor Huang Yadong of the Gladstone Institute said
.
▲Professor Huang Yadong (photo source: Gladstone Institute official website) Based on these findings, Professor Huang Yadong and his colleagues are planning to cooperate with multiple medical centers to initiate clinical trials using bumetanide to treat patients with Alzheimer’s disease.
Start with patients who carry the APOE4 allele
.
The researchers also warned that doctors should not give bumetanide to patients until the efficacy of the drug is confirmed in clinical trials
.
"Our research emphasizes the power of combining'old medicines and new uses' with precision therapy, and at the same time shows the usefulness of using existing experiments and real-world data for rapid and early verification," said Professor Huang.
"This may be for the Alzheimer's Murder disease and other complex age-related diseases are a highly effective strategy for finding better treatments
.
Source of title picture: 123RF Reference material: [1] Mouse experiments with a decades-old drug suggest a new approach to Alzheimer's treatment.
Retrieved October 11, 2021, from https:// /mouse-experiments-with-old-drug-suggest-new-approach-to-alzheimers-treatment/[2] Taubes et al.
, (2021).
Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4- related Alzheimer's disease.
Nature Aging, https://doi.
org/10.
1038/s43587-021-00122-7[3] Can an Already Approved Drug Treat Alzheimer's Disease? Retrieved October 11, 2021, from https://gladstone.
org /news/can-already-approved-drug-treat-alzheimers-disease Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
.
This article is for information exchange purposes only.
The views in the article do not represent WuXi AppTec’s position.
It does not mean that WuXi AppTec supports or opposes the views
in the
article .
This article is not a treatment plan recommendation
.
If you need treatment plan guidance, please go to a regular hospital
.
It has a profound impact on patients, their families, and society
.
Moreover, the progress of drug development in this field is slow, and it is urgent to explore innovative strategies for new drug development
.
In a study published in Nature Aging today, the team of Professor Huang Yadong from the Gladstone Institutes in the United States found that an "old drug" that has been on the market for nearly 40 years can relieve cognition in animal experiments And learning deficits
.
And analysis of real-world patient data using this drug shows that among the elderly over 65, people who regularly take this drug have a 35%-75% reduction in the risk of developing Alzheimer's disease
.
The researchers pointed out that the results of this study reveal a new strategy for drug development
.
The development of new drugs for complex diseases such as Alzheimer's disease has always been a time-consuming and labor-intensive process
.
In order to bring safe and effective therapies to patients faster, the Gladstone Institute launched the Gladstone Center for Translational Advancement in 2017 to explore new uses of "old drugs" that have been approved by the FDA
.
The primary goal of this center is to develop treatments for Alzheimer's disease.
Due to the complexity of its etiology, the strategy adopted by the research team does not target specific signaling pathways, but comprehensively detects differences in gene expression between patients and healthy people.
, Including patients with different APOE alleles
.
The different forms of the APOE gene are one of the most important genetic risk factors for Alzheimer's disease.
People who carry two APOE4 alleles have an increased risk of 12-14 compared with those who do not carry APOE4 alleles.
Times! The researchers found that the expression levels of nearly 2,000 genes in patients changed, and about 6% of the genes had similar changes in patients carrying different combinations of APOE3 and APOE4 alleles
.
▲Similar gene expression changes were found in Alzheimer's disease patients carrying different combinations of APOE3 and APOE4 alleles (picture source: reference [2]).
Then, the researchers conducted a study on more than 1,300 approved drugs.
After screening, take a look at which drugs can reverse these changes in gene expression
.
The screening results found a drug called bumetanide, which is a diuretic that has been used in the past few decades to reduce edema caused by heart failure, liver or kidney disease
.
Bumetanide can regulate the ability of cells to absorb sodium and chloride ions.
In addition to regulating the body's water balance, it also plays an important role in transmitting electrical signals to nerve cells in the brain
.
In a mouse model of Alzheimer's disease carrying two APOE4 alleles, scientists found that bumetanide can significantly delay the onset of Alzheimer's disease symptoms
.
Usually these mice developed learning and memory deficits at 15 months (equivalent to 60 years old in humans), but the animals treated with bumetanide did not develop these deficits
.
In addition, in another mouse model, bumetanide treatment also reduced the degree of amyloid deposition in the animal's hippocampus (one of the key areas in the brain for memory production)
.
▲The treatment of bumetanide (right) reduces the deposition level of amyloid in Alzheimer's disease mouse model (picture source: reference [2]) Traditional drug development is after animal research, usually in human clinical The safety of the drug is tested in detail in the trial
.
However, bumetanide has been approved by the FDA, which allows researchers to analyze its use data in the real world and observe its possible therapeutic effects
.
Researchers analyzed the patient databases of the University of California, San Francisco (UCSF) and Mount Sinai Health System (Mount Sinai Health System) and found more than 3,700 bumetanide over the age of 65
.
Then compare them with the incidence of Alzheimer's disease in elderly people of similar age and health, but using other diuretics
.
Researchers have found that patients taking bumetanide have a 35% to 75% reduction in disease risk
.
▲The risk of Alzheimer's disease in elderly people taking bumetanide is significantly reduced (picture source: reference [3]) "These two electronic health record databases did not affect patients based on their APOE allele characteristics.
Classification, which means that bumetanide may benefit a wide range of patients who carry two APOE4 alleles
.
"Senior author of this study and senior researcher Professor Huang Yadong of the Gladstone Institute said
.
▲Professor Huang Yadong (photo source: Gladstone Institute official website) Based on these findings, Professor Huang Yadong and his colleagues are planning to cooperate with multiple medical centers to initiate clinical trials using bumetanide to treat patients with Alzheimer’s disease.
Start with patients who carry the APOE4 allele
.
The researchers also warned that doctors should not give bumetanide to patients until the efficacy of the drug is confirmed in clinical trials
.
"Our research emphasizes the power of combining'old medicines and new uses' with precision therapy, and at the same time shows the usefulness of using existing experiments and real-world data for rapid and early verification," said Professor Huang.
"This may be for the Alzheimer's Murder disease and other complex age-related diseases are a highly effective strategy for finding better treatments
.
Source of title picture: 123RF Reference material: [1] Mouse experiments with a decades-old drug suggest a new approach to Alzheimer's treatment.
Retrieved October 11, 2021, from https:// /mouse-experiments-with-old-drug-suggest-new-approach-to-alzheimers-treatment/[2] Taubes et al.
, (2021).
Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4- related Alzheimer's disease.
Nature Aging, https://doi.
org/10.
1038/s43587-021-00122-7[3] Can an Already Approved Drug Treat Alzheimer's Disease? Retrieved October 11, 2021, from https://gladstone.
org /news/can-already-approved-drug-treat-alzheimers-disease Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
.
This article is for information exchange purposes only.
The views in the article do not represent WuXi AppTec’s position.
It does not mean that WuXi AppTec supports or opposes the views
in the
article .
This article is not a treatment plan recommendation
.
If you need treatment plan guidance, please go to a regular hospital
.
